Influence of interferon β-1a dose frequency on PBMC cytokine secretion and biological effect markers

Interferon-beta regimens for immune-mediated diseases, such as multiple sclerosis (MS), have not been compared regarding their biological effects. In this randomized, parallel-group, placebo-controlled study, cytokine secretion by mitogen-stimulated PBMCs and serum response markers were assessed in volunteers receiving subcutaneous recombinant IFN beta-la (Rebif(R), Ares-Serono) 22 mu g once a week (QW), 22 mu g three times a week, 66 mu g QW, or placebo. The production of IL-1 beta, IL-6, IFN-gamma, TNF-alpha and TNF-alpha markedly decreased during 24-48 h after each injection, with limited dose-dependency and no evidence of tolerance or effect augmentation over 1 month. IL-IO secretion remained unchanged. The increase in serum beta(2)(_)microglobulin, neopterin and 2-5A-synthetase was more sustained. Thus, IFN-beta-induced immunomodulation in vivo strongly depends on the administration schedule, the time-integrated effect being 2-3 times greater when a same weekly dose is divided is in three injections. (C)1999 Elsevier Science B.V. All rights reserved.